Abstract:
:Structure-activity relationships for rigid analogues of combretastatin A-4 (CA-4) were investigated, leading to the discovery of a series of 3,4-diaryl-1,2,5-oxadiazole-N-oxides. Among them, 7n' and 7n'' showed remarkable antiproliferative activities against three cancer cell lines in nanomolar concentrations. Interestingly, 7n' inhibited tubulin polymerization much more efficiently than CA-4. Cellular mechanism investigation elucidated 7n' disrupted the cellular microtubule structure, arrested cell cycle at G2/M phase and induces apoptosis. Molecular modeling study revealed 1,2,5-oxadiazole-N-oxide ring could increase a hydrogen bond interaction with the binding site. These results provide impetus and further guidance for the development of new CA-4 analogues.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Hong Y,Zhao Y,Yang L,Gao M,Li L,Man S,Wang Z,Guan Q,Bao K,Zuo D,Wu Y,Zhang Wdoi
10.1016/j.ejmech.2019.05.036subject
Has Abstractpub_date
2019-09-15 00:00:00pages
287-296eissn
0223-5234issn
1768-3254pii
S0223-5234(19)30446-5journal_volume
178pub_type
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